The standard SA-beta-gal staining, while indicative of the presence of senescent cells, is not an absolute marker for senescent cell and indicates increased lysosmal b-galactosidase activity. The use of several molecular markers that represent different characteristics of senescent cells is necessary (see figure). Such molecular markers can represent the cell cycle arrest machinery (e.g. p53, p21, p16), lack of cellular proliferation (e.g. lack of BrdU incorporation, Ki67), activation of the DDR (e.g. gamamH2AX or p53BP1 foci), expression of secretory factors (e.g. IL-6 and IL-8), the activation of the pathways that regulate the secretory phenotype (e.g. p-p65 or p-p38), the activation of immune surveillance-related genes and possible regulators for their pro-survival response (DCR2, p-Akt, p-Erk).

Abstract

Cellular senescence, a permanent state of cell cycle arrest accompanied by a complex phenotype, is an essential mechanism that limits tumorigenesis and tissue damage. In physiological conditions, senescent cells can be removed by the immune system, facilitating tumor suppression and wound healing. However, as we age, senescent cells accumulate in tissues, either because an aging immune system fails to remove them, the rate of senescent cell formation is elevated, or both. If senescent cells persist in tissues, they have the potential to paradoxically promote pathological conditions. Cellular senescence is associated with an enhanced pro-survival phenotype, which most likely promotes persistence of senescent cells in vivo. This phenotype may have evolved to favor facilitation of a short-term wound healing, followed by the elimination of senescent cells by the immune system. In this review, we provide a perspective on the triggers, mechanisms and physiological as well as pathological consequences of senescent cells.